Zwitterionic drugs have poor absorption through intact skin due to their rather large dipole moments and their resulting low lipid solubility. In general, salts of organic compounds have lower skin permeation than their corresponding free acids or bases. The unionized acids and bases can take advantage of lipophilic pathways through the skin that ionic species cannot. Typical non-zwitterionic acidic or basic substances can be placed in transdermal formulations at appropriate pHs such that the active agent is substantially in the non-ionic form leading to enhanced absorption through human skin.
Unfortunately, zwitterionic drugs cannot be made non-ionic. At all pHs, at least one ionic group is present. For example, at pHs higher than the pKa of the acidic group(s) of a zwitterion, the acidic group is charged; at pHs lower than the pKa of the basic group(s) of a zwitterion, the basic group is charged. At pHs close to the zwitterion pI, both groups are charged. Amino acid containing drugs, being the zwitterions of greatest interest, remain charged at all pHs in the range of 2.0 to 11 suitable for transdermal application. It would not be expected that one could achieve a suitable flux of a zwitterion through skin to make transdermal administration thereof practical.
A number of transdermal devices are disclosed in the following U.S. Patents, all of which are incorporated herein by reference: U.S. Pat. Nos. 4,605,670, 3,551,554, 4,677,131, 3,472,931, 4,132,781, 4,557,943, 4,130,667, 3,952,099, 4,046,886, 4,299,826, 4,764,379, 4,379,454, 4,144,317, and 3,948,262 to name a few.